It has been previously shown that the activity of the neonatal Genioglossus(GG) muscle reflexly increases only in response to large amounts of upper airway negative pressure (UANP) in lambs (Duara, Ped Res: 4:331A,1994), in comparison to the small amounts needed to activate the GG in adults. In order to evaluate maturation of the UANP reflex in lambs, we hypothesized that onset of the adult pattern would coincide with the onset of another developmental marker, namely rumination, at 3-4 weeks of age. Because hypoxia increases respiratory muscles activity, we also hypothesized that hypoxia would potentiate the UANP reflex. Therefore, we studied seven chronically instrumented lambs shortly after birth (study 1: mean±SD age 10.6±0.48 days & weight 5.47±0.43 kg) and again at approximately 1 month of age (study 2: mean±SD age 25.1 ± 0.7 days & weight 8.14 ± 0.43 kg). During surgery, EMG wires were placed in the diaphragm and GG and a mid-cervical tracheal stoma was created. The animals were allowed to recover for 24-48 hours prior to study 1. Isolated upper airways (UA) were evaluated while awake lambs were allowed to breathe through tracheostomies. End-expiratory NP of different magnitudes (-5, -10,-20, -40 cm H2O) were randomly applied to the isolated UA for 3 breaths, or 3 seconds if apnea was induced, in room air (RA) and hypoxia (10% O2 through the tracheostomy for 7-10 min). EMG activity of the GG was quantified as average activity (AvAc, area under the curve/duration) derived from the moving time average of phasic EMG output. Results revealed that there was a significant increase in the GG response in relationship to increasing magnitudes of UANP in both study 1 and study 2 (p<0.05). Hypoxia induced a significant increase in GG activity in both studies (<0.05). However, there was no significant increase in GG activity with small amounts of NP (-5 cm H2O) in either study, and hypoxia did not potentiate augmentation of GG at this level of NP. We conclude that the UANP reflex remains relatively immature in ruminating lambs, and that the adult response to low magnitude NP must occur later in development. Hypoxia augmented GG muscle activity above basal values in both studies, but did not potentiate its response to low magnitude NP. We speculate that the immature UANP reflex in neonates contributes to impaired oropharyngeal airway reopening in the event of its closure, and the failure to augment reflex activation with hypoxia may be a contributory factor in certain instances of SIDS.